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OBJECTIVES Estimation of liver fat among living donor candidates is necessary before living donor liver transplant. This study aimed to investigate the usefulness of the controlled attenuation parameter compared with liver biopsy for pretransplant estimation of hepatic steatosis in living liver donors. MATERIALS AND METHODS In this retrospective study, we included all individuals who underwent transient elastography with controlled attenuation parameter and ultrasonography-guided liver biopsy as a part of donor evaluations before living donor liver transplant. Clinical and laboratory data of living donor candidates were reviewed and collected. RESULTS Of 49 donor candidates included in this study, 21 (42.9%) had different degrees of hepatic macrosteatosis. Of the 21 donor candidates who had hepatic steatosis in liver biopsy, 13 individuals were diagnosed to have steatosis in transient elastography. Of the 28 donor candidates without hepatic steatosis in liver biopsy, 26 individuals showed no steatosis in transient elastography (odds ratio: 21.12; 95% CI, 3.91- 114.08; P < .001). Controlled attenuation parameter was useful in discriminating presence (P = .001) and grade of hepatic steatosis (P = .009) compared with liver biopsy with good sensitivity and specificity. CONCLUSIONS The controlled attenuation parameter is a noninvasive method for detection of hepatic steatosis in living donor candidates and can be used as an adjunct to liver biopsy for screening of living donor candidates before liver transplant.

OBJECTIVES Nonalcoholic fatty liver disease is a rapidly growing disease and is hypothesized to become the most common cause of liver cirrhosis in the near future. This study aimed to investigate trends of nonalcoholic steatohepatitis as an indication for liver transplant in Iranian patients. MATERIALS AND METHODS Liver transplant data from all adult patients (age > 18 y) who had undergone liver transplant between 1993 and 2017 at the Shiraz Organ Transplant Center (Shiraz, Iran) were reviewed. Underlying liver diseases leading to liver transplant were stratified according to year of transplant, and trends of increase or decline were analyzed. Kaplan-Meier curves were used for analysis of posttransplant survival of patients with nonalcoholic steatohepatitis and patients with modified nonalcoholic steatohepatitis. RESULTS We evaluated 3184 liver transplant patients. Of these, 112 patients with biopsy-proven nonalcoholic steatohepatitis underwent liver transplant up to the end of 2017. Mean age of patients was 52.86 ± 9.01 years in those with nonalcoholic steatohepatitis and 51.73 ± 7.91 years in those with modified nonalcoholic steatohepatitis (P > .05).The prevalence of nonalcoholic steatohepatitis as an indication for liver transplant was 0.8% in 2011, 0.36% in 2012, 1.9% in 2013, 4.01% in 2014, 2.89% in 2015, 6.65% in 2016, and 9.97% in 2017. The prevalence of modified nonalcoholic steatohepatitis was 2.4% in 2011, 2.88% in 2012, 2.71% in 2013, 2% in 2014, 2.17% in 2015, 2.13% in 2016, and 2.28% in 2017. We found that nonalcoholic steatohepatitis as a cause of liver transplant increased significantly during recent years (P < .001). CONCLUSIONS Nonalcoholic steatohepatitis is a rapidly growing indication for liver transplant among Iranian patients. Health care providers should consider programs for prevention and early diagnosis of patients with nonalcoholic steatohepatitis for proper treatment.

OBJECTIVES Detection of hepatic steatosis in donors is an important step for selection of a suitable liver allograft in living-donor transplant. This study aimed to investigate the role of hepatic computed tomography volumetry as a noninvasive method for detection of hepatic steatosis in living liver donors. MATERIALS AND METHODS In a cross-sectional study, individuals who had undergone liver biopsy as a pretransplant checkup before living-donor liver transplant were included. The segmental liver volumes were measured by computed tomography scan with intravenous contrast enhancement. RESULTS Our study included 179 individuals. Mean total volume of the liver was 1705.2 ± 256.5 cm3 in those with steatohepatitis and 1419.4 ± 241.2 cm3 in those without steatohepatitis (P < .001). Higher total volume of the liver (odds ratio of 1.005; 95% confidence interval, 1.001-1.010; P = .012) and total liver volume-to-standard liver volume ratio (odds ratio of 1.090; 95% confidence interval, 1.021-1.163; P = .009) were independent predictors of steatohepatitis. A cutoff value of 1531 cm3 for total liver volume was a predictor of presence of steatohepatitis in liver biopsies of donors (sensitivity = 83%; specificity = 71%; area under the curve = 0.809; P < .001). CONCLUSIONS Computed tomography volumetry may be considered as an auxiliary noninvasive method for estimation of hepatic steatosis/steatohepatitis and may be used as a guide to select donor candidates for liver biopsy.

Objectives Survival after liver transplant depends on pretransplant, peritransplant, and posttransplant factors. Identifying effective factors for patient survival after transplant can help transplant centers make better decisions. Materials and methods Our study included 902 adults who received livers from deceased donors from March 2011 to March 2014 at the Shiraz Organ Transplant Center (Shiraz, Iran). In a 3-step feature selection method, effective features of 6-month survival were extracted by (1) F statistics, Pearson chi-square, and likelihood ratio chi-square and by (2) 5 machine-learning techniques. To evaluate the performance of the machine-learning techniques, Cox regression was applied to the data set. Evaluations were based on the area under the receiver operating characteristic curve and sensitivity of models. (3) We also constructed a model using all factors identified in the previous step. Results The model predicted survival based on 26 identified effective factors. In the following order, graft failure, Aspergillus infection, acute renal failure and vascular complications after transplant, as well as graft failure diagnosis interval, previous diabetes mellitus, Model for End-Stage Liver Disease score, donor inotropic support, units of packed cell received, and previous recipient dialysis, were found to be predictive factors in patient survival. The area under the receiver operating characteristic curve and model sensitivity were 0.90 and 0.81, respectively. Conclusions Data mining analyses can help identify effective features of patient survival after liver transplant and build models with equal or higher performance than Cox regression. The order of influential factors identified with the machine-learning model was close to clinical experiments.

In some cases of liver transplant, standard hepatic artery reconstruction may be difficult or impossible due to inadequate flow of the recipient's hepatic artery, as a result of stenosis, intimal dissection, or anomalies of the hepatic artery. We compared splenic artery transposition with extra-anatomic jump graft as 2 alternative methods for hepatic artery reconstruction in these situations.We reviewed the files of 2135 liver transplant recipients from March 2011 to February 2016 at the Shiraz Transplant Center. Data of 93 patients with unusual hepatic artery reconstruction were analyzed to assess outcomes, morbidity, mortality, and pre- and posttransplant parameters (both clinical and paraclinical). Patients were divided into 2 groups: 17 with splenic artery transposition (splenic artery group) and 76 with extra-anatomic jump grafts (control group).There was only 1 occurrence (5.8%) of hepatic artery thrombosis in the splenic artery group causing extra-anatomic jump graft. However, in the control group, there were 4 occurrences (5.2%) of hepatic artery thrombosis, causing 1 revision of anastomosis and 3 retransplant procedures. No deaths due to hepatic artery complications were reported in the 2 groups. Three-year survival rate was 87.5% in the splenic artery group and 68.9% in the control group.Splenic artery transposition is an acceptable method for hepatic artery reconstruction in deceased-donor liver transplant procedures with no greater rates of complication or morbidity than extra-anatomic jump grafts. Less operation time and better exposure during surgery are advantages of this method.

Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients.We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism.Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02).Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

To identify the predictors of overall survival and tumor-free survival of 88 hepatocellular carcinoma patients who were treated with orthotopic liver transplant at Shiraz Organ Transplant Center.We performed this retrospective study after reviewing the transplant database of all patients who underwent orthotopic liver transplant secondary to hepatocellular carcinoma and liver cirrhosis. Hepatocellular carcinoma was diagnosed in 70 patients before liver transplant and 18 patients on histologic examination of the explanted livers. Cox regression identified independent factors that affected posttransplant survival.The overall survival rate was 83% and the tumor-free survival rate was 79.5%. Independent factors for tumor recurrence were Milan criteria, alpha-fetoprotein level before operation ≥ 400 ng/mL, tumor grade, vascular invasion, and age. Vascular invasion (odds ratio, 5; 95% confidence interval, 1.1 to 25.496; P = .049) and tumor grade (odds ratio, 14.42; 95% confidence interval, 3.652 to 56.95; P.001 were statistically significant.Vascular invasion and tumor grade were predictive factors for tumor-free survival.

This study sought to evaluate in pediatric liver transplant recipients the effects of hybrid antiviral therapy on the rate of posttransplant lymphoproliferative disorder.All pediatric patients (87 cases) who had undergone a liver transplant between April 2011 and March 2012 took part in the study and received hybrid antiviral treatment (case group). Epstein-Barr virus polymerase chain reaction was monitored intermittently. The results were compared to those of a historical control group including 117 pediatric patients who received a liver transplant between April 2009 and March 2011. Follow-up was 27 to 47 months in the control group and 12 to 26 months in the case group.Posttransplant lymphoproliferative disorder occurred in 12 patients in control group (10.2%) and 5 patients in case group (5.7%) (P = .249). Of 12 cases of posttransplant lymphoproliferative disorder, death occurred in 5 cases in the control group (41.7%), while no posttransplant lymphoproliferative disorder-associated death was seen in the case group (P = .086).Although hybrid antiviral treatment did not result in a statistically significant decrease in posttransplant lymphoproliferative disorder and posttransplant lymphoproliferative disorder-associated mortality rates, considering the limited number of posttransplant lymphoproliferative disorder cases in this study, this decrease may be interpreted as noticeable, and we advise using this strategy for pediatric patients undergoing a liver transplant.

A 50-year-old man sustained blunt abdominal trauma in a motor vehicle accident. He underwent exploratory laparotomy on the day of trauma, and severe bleeding from the base of the small bowel mesentery was controlled by mass ligation and through-and-through suturing. After transfer to our center, repeat exploratory laparotomy showed ischemic small intestine, ischemic right colon, and severe pancreatic trauma. The severely injured organs were excised including the entire small bowel, pancreas, spleen, stomach, and right hemicolon. The next day, a modified multivisceral transplant was performed including stomach, pancreaticoduodenal complex, and small bowel transplant. Postoperative complications included an intra-abdominal collection that was drained percutaneously with ultrasonographic guidance and severe rejection that was treated with anti-thymocyte globulin. In summary, for select patients who have severe abdominal trauma may be treated with acute multivisceral transplant.

Patients who have liver transplant are at high risk of developing de novo malignancies. The purpose of this study was to evaluate incidence and histologic type of de novo malignancies after liver transplant in a liver transplant center.In 1700 patients who had orthotopic liver transplant from deceased and living donors from January 1992 to October 2012, de novo malignancies after transplant were analyzed.There were 38 patients (2.2%) who developed de novo malignancy. Pathologic diagnosis was posttransplant lymphoproliferative disorder in 24 patients (63%), gastrointestinal adenocarcinoma in 4 patients (10%), Kaposi sarcoma in 3 patients (8%), pancreatic head adenocarcinoma in 2 patients (5%), papillary thyroid carcinoma in 1 patient (3%), lumbosacral multiple myeloma in 1 patient (3%), conjunctive carcinoma in 1 patient (3%), testicular cancer in 1 patient (3%), and metastatic adenocarcinoma to the vertebrae of unknown origin in 1 patient (3%). In the 24 patients who had posttransplant lymphoproliferative disorder, 20 patients (83%) were children aged10 years, and 5 patients (21%) died of this disease.Posttransplant lymphoproliferative disorder was the most common malignancy among liver transplant recipients. This disease primarily involved children and was a major cause of morbidity and mortality. Preventive and early diagnostic strategies are justified to decrease morbidity and mortality from de novo malignancy after liver transplant.

This study sought to investigate discarded organs at the Shiraz University of Medical Sciences, Shiraz, Iran.We performed a retrospective analysis of Shiraz Transplant Center database regarding discarded organ during May 2010 and December 2013. Our study investigated 80 unused liver donors' characteristics. The data included age, sex, cause of discard, cause of brain death, hypotension during hospitalization of donors, and result of liver biopsy.Among 780 grafts, 80 livers (10.25%), between May 2010 and December 2013, were unsuitable for transplant. Among the donors whose livers were discarded, 36 were women (45%) and 44 were men (55%) (mean age, 43.7 ± 14 years; range, 1-67 y). The most common causes of brain death were cerebrovascular accidents 27 (33.8%), trauma 27 (33.8%), aneurysm, and subarachnoid hemorrhage 13 (16.3%). The most common cause of unused organ were fatty liver 50 (62.5%) and necrosis 25 (31%) (steatosis more than 40%).Old age, cerebrovascular accidents, and severe steatosis ≥ 40 were the most common associated factors in organ discard in this study.

Neurologic complications are a significant cause of morbidity in children after liver transplant. In this study, we sought to evaluate the neurologic complications in children after liver transplant.All children aged younger than 18 years old who had undergone liver transplant between June 2004 and June 2007 were included in this prospective study. There were 30 boys (62.5%) and 18 girls (37.5%) (mean age, 9.6 -/+ 4.3 years; mean duration of follow-up, 21.6 -/+ 9.4 months). The most common indications for liver transplant were biliary atresia (n=12, 25%), Wilson disease (n=7, 14.6%), tyrosinemia (n=7, 14.6%), progressive familial intrahepatic cholestasis (n=6, 12.5%), and autoimmune cirrhosis (n=5, 10.4%).Immunosuppressive medication consisted tacrolimus (n=44, 91.7%) or cyclosporine (n=4, 8.3%) combined with mycophenolate mofetil (n=33, 68.7%) and prednisolone (n=18, 37.5%). The most-common neurologic complications were tremor (n=8, 16.7%), convulsions (n=6, 12.5%), insomnia (n=6, 12.5%), headache (n=5, 10.4%), muscle cramps (n=5, 10.4%), paresthesia (n=3, 6.2%), and weakness (n=3, 6.2%).We conclude that the most-common neurologic complication after liver transplant in children in contrast to other studies is tremor, same as adult patients. This may be due to higher rate of use of tacrolimus in our patients.

The classic technique for orthotopic liver transplant consists of the total excision of the retrohepatic inferior vena cava during native hepatectomy. Controversy about the effects of the classic technique on postoperative renal function continues. The aim of this study was to evaluate the effects of the chosen hepatectomy technique on postoperative renal function.Of 253 patients who received an orthotopic liver transplant between June 2006 and July 2008 in the Shiraz transplant unit, only 15 underwent operation with the classic technique. Patient demographics and factors including cold ischemic time, warm ischemic time, operative time, transfusions, blood loss, and early postoperative renal function were assessed retrospectively. The criteria for acute renal failure were a serum creatinine level of133 micromol/L (1.5 mg/dL), an increase in the baseline serum creatinine level by 50%, or oliguria requiring renal replacement therapy.All patients received a liver from a deceased donor, and none required venovenous bypass during the operation. The minimum mean arterial blood pressure value of the patients during clamping was 65 -/+ 19 mm Hg. The mean preoperative plasma creatinine level was 87.51 -/+ 39.78 micromol (0.99 -/+ 0.45 mg/dL). During the first week after transplant, 7 patients (46.6%) experienced acute renal failure, and 3 of those 7 required renal replacement therapy. By the sixth postsurgical month, 4 of those 7 patients had died (1 from adult respiratory distress syndrome, 2 from sepsis, and 1 from recurrent cholangiocarcinoma). In all other patients, the plasma creatinine level had returned to the normal range by the third postsurgical week 3 or during short-term follow-up.Use of the classic technique for orthotopic liver transplant may increase the rate of postoperative renal failure, but that complication usually resolves during short-term follow-up.

Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients.Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist.Of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P.05).D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.